In outbred populations pregnancies represent confrontation of females by allografts which are unique in being consistently successful. Although the fetus' success as an allograft turn in part upon unique quarantining properties of its trophoblast, immunoregulatory processes in the mother provide important ancillary protective mechanisms. That gestating mothers are immunologically cognizant of alien fetuses in their uteri is of evidence by: 1) hypertrophy, on an immunogenetically specific basis of the lymph nodes draining the uterus and to a lesser extent of the spleen, and 2) the emergence of a "muted" population of sensitized lymphocytes demonstrable on the basis of GVH or adoptive transfer assay, and 3) the appearance of hemagglutinins and lymphocytotoxic antibodies in their blood. The immunity evoked in the pregnant female is noncytopathogenic to the conceptus and its full development and expresstion actually contributes to the intra-uterine growth rate of the fetal allograft. On the basis of these observations from our own laboratories, we believe that pregnancy offers a unique experimental situation for the study of blocking or control factors that exert powerful inhibitory influences on the development and deployment of cellular immunity not only to fetuses but to transplantation antigens, to tumor specific as well as autoantigens, and possibly facilitate the induction of tolerance in adult subjects. The overall objective of the proposed research is to utilize both sophisticated in vivo as well as in vitro models, side by side, to help elucidate the immunoregulatory processes, both humoral and cellular, operational during pregnancy that lead to both specific and non-specific suppression and/or facilitation of maternal cell mediated hypersensitivity. Our aim also, is to define the roles of pregnancy induced humoral factors as well as cellular effectors in the abrogation of graft-versus-host disease and in the phenomenon of immunologic tolerance.